Cell Survival Programs and Ischemia /Reperfusion: Hormesis, Preconditioning, and Cardioprotection

Abstract

ii This e-book is an original work commissioned for the Colloquium Digital Library of Life Sciences, a curated collection of time-saving pedagogical resources for researchers and students who want to quickly get up to speed in a new area of life science/biomedical research. Each e-book available in Colloquium is an in-depth overview of a fast-moving or fundamental area of research, authored by a prominent contributor to the field. We call these resources 'Lectures' because authors are asked to provide an authoritative, state-of-the-art overview of their area of expertise, in a manner that is accessible to a broad, diverse audience of scientists (similar to a plenary or keynote lecture at a symposium/meeting/colloquium). Readers are invited to keep current with advances in various disciplines, gain insight into fields other than their own, and refresh their understanding of core concepts in cell & molecular biology. Physiology is a scientific discipline devoted to understanding the functions of the body. It addresses function at multiple levels, including molecular, cellular, organ, and system. An appreciation of the processes that occur at each level is necessary to understand function in health and the dysfunction associated with disease. Homeostasis and integration are fundamental principles of physiology that account for the relative constancy of organ processes and bodily function even in the face of substantial environmental changes. This constancy results from integrative, cooperative interactions of chemical and electrical signaling processes within and between cells, organs and systems. This eBook series on the broad field of physiology covers the major organ systems from an integrative perspective that addresses the molecular and cellular processes that contribute to homeostasis. Material on pathophysiology is also included throughout the eBooks. The state-of the-art treatises were produced by leading experts in the field of physiology. Each eBook includes stand-alone information and is intended to be of value to students, scientists, and clinicians in the biomedical sciences. Since physiological concepts are an ever-changing work-in-progress, each contributor will have the opportunity to make periodic updates of the covered material.Published titles (for future titles please see the website, www.morganclaypool.com/page/lifesci) ABSTRACTThe major purpose of this book is to review the evidence supporting the concept that intrinsic cell survival programs can be activated by a variety of mildly noxious stimuli or pharmacologic agents to confer protection against the deleterious effects of ischemia/reperfusion (I/R). We begin with a discussion of the concept of hormesis (a term used most extensively in the toxicologic literature which refers to biphasic cellular responses that depend on concentration or intensity of a stimulus), review the seminal studies that led to the discovery of the cardioprotective effects of ischemic preconditioning, and outline its therapeutic potential (Chapter 1). This is followed ...

Ischemia/Reperfusion

“…Of these diverse serine-threonine kinase isotypes, PKCδ and PKCε are the most important in the context of I/R, with the former playing an important role in I/R injury, while the latter is a major contributor in the cardioprotective mechanism underlying pre-and postconditioning (148, 172, 449, 721, 746). With regard to the role of PKCδ, translocation and activation of this isoform occurs in response to I/R (305, 443, 746).…”

Intravital Microscopic Methods to Evaluate Anti-inflammatory Effects and Signaling Mechanisms Evoked by Hydrogen Sulfide

“…Preconditioning refers to a phenomenon where antecedent exposure to a particular stimulus confers protection against the deleterious effects induced by subsequent exposure to prolonged I/R (Krenz, Baines, Kalogeris, & Korthuis, 2013). Preconditioning stimuli typically produce two phases of protection in I/R.…”

“…Acute or early phase preconditioning develops rapidly (within minutes), involves activation of pre-existing effector molecules, and is short-lived, conferring protection for 2–6 h before disappearing. Delayed acquisition of tolerance to ischemia (late phase preconditioning) arises 12–24 h after the initial preconditioning stimulus is applied, is longer lived (24 h or longer), and requires expression of new gene products to mediate protection (Krenz et al, 2013). …”

“…The observations that H 2 S donors produce vasodilation by activation of K ATP channels and enhances the vasorelaxant effects of NO (Wang, 2003, 2012), coupled with the fact that K ATP channel activators and NO donors elicit preconditioning (Krenz et al, 2013), led us to postulate that this gaseous signaling molecule could also serve as a preconditioning stimulus to limit the proinflammatory effects of I/R (Yusof, Kamada, Kalogeris, Gaskin, & Korthuis, 2009). To address this issue, we first sought to determine whether and H 2 S donor (NaHS) preconditioning would elicit anti-inflammatory effects in tissues exposed to I/R one (acute preconditioning) or 24 h (delayed preconditioning) after NaHS treatment.…”

HORMESIS: A Fundamental Concept with Widespread Biological and Biomedical Applications

“…Once there is sufficient systemic adaptive pathway degradation, life itself can become threatened. Considerable work is now underway to assess whether poor functioning pathways can be revitalized via the use of a higher dose, activation of greater numbers of receptors or other means [50]. Thus, hormesis is a fundamental biological concept central to evolutionary biology, public health, human performance, clinical medicine, longevity, the aging process and to the end of life as well.…”